1. Field of the Invention
The invention relates to methods for identifying therapeutic agents for the treatment of osteoporosis and as serum lipid lowering agents. The invention relates to isolating, cloning and using nucleic acids comprising the promoter regions of mammalian transforming growth factor B genes that are novel regulatory elements designated "raloxifene responsive elements". The invention also encompasses genetically engineered eukaryotic cells containing the recombinant expression constructs wherein the raloxifene responsive elements are operably linked to reporter genes. In such cells the raloxifene responsive elements are capable of modulating transcription of the reporter genes and response to treatment with certain compounds. The invention also relates to methods for identifying anti-osteoporosis agents that induce transcription of certain genes via raloxifene responsive elements and that specifically do not induce deleterious or undesirable side effects that have been associated with estrogen replacement therapy, such as increased risk with uterine and breast cancer. The nucleic acids, cells and methods of the invention provide effective methods for screening putative sources of anti-osteoporosis agents or serum lipid lowering agents and identifying those that advantageously lack the undesirable side effects associated with current anti-osteoporosis agents.
2. Background of the Related Art
In 1991, U.S. pharmaceutical companies spent an estimated $7.9 billion on research and development devoted to identifying new therapeutic agents (Pharmaceutical Manufacturer's Association). The magnitude of this amount is due, in part, to the fact that the hundreds, if not thousands, of chemical compounds must be tested in order to identify a single effective therapeutic agent that does not engender unacceptable levels of undesirable or deleterious side effects. There is an increasing for economical methods of testing large numbers of testing large number of chemical compounds to quickly identify those compounds that are likely to be effective in treating disease. At present, few such economical systems exist.